Estudios que sustentan la utilización de los GLP1 AR en los pacientes con DM2

Por Dr. Henry Mauricio. Especialista en Medicina Interna

En la diabetes, al momento de indicar un medicamento, el médico tratante tomará en cuenta diferentes factores:

• Las metas establecidas
• La posibilidad real de administración
• Los efectos adversos del fármaco en cuestión
• Económicos

Estos factores ayudan no solamente con la claridad de la prescripción de una familia de fármacos, sino a escoger adecuadamente uno específico y afinar aún más los resultados con la dosis adecuada, ya que los efectos también son dosis dependientes en algunos de ellos.

Debido a los múltiples beneficios que demuestran los fármacos AR GLP1 en los campos metabólico, cardiovascular y renal, se van diseñando estudios que ponen a prueba sus efectos junto o contra placebo, metformina, sulfonilureas, insulina e incluso, otros fármacos pertenecientes a su misma familia (head-to-head). Esto ha generado una literatura tan extensa en tan pocos años, que la sola búsqueda de cada uno de los estudios es realmente extenuante. Aunado a esto, cada estudio también es llevado a formar parte de metanálisis y a discusiones, sesiones de mesas de expertos y discusiones de guías: demasiado para digerir.

A continuación, enumero los AR GLP1 y facilito sus DOI (Digital Object Identifier) o bien, sus direcciones de publicación.

• Liraglutide
  • LEADER (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). Publicación: https://www.nejm.org/doi/full/10.1056/NEJMoa1603827
  • ELLIPSE (Efficacy and Safety of Liraglutide in Combination With Metformin Compared to Metformin Alone, in Children and Adolescents With Type 2 Diabetes). Publicación: https://www.nejm.org/doi/full/10.1056/NEJMoa1903822
• Dulaglutide
  • AWARD-1 (Efficacy and Safety of Dulaglutide Added Onto Pioglitazone and Metformin Versus Exenatide in Type 2 Diabetes in a Randomized Controlled Trial). Publicación: https://care.diabetesjournals.org/content/37/8/2159
  • AWARD-2 (Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride). Publicación: https://care.diabetesjournals.org/content/38/12/2241
  • AWARD-3 (Efficacy and Safety of Dulaglutide Monotherapy Versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial). Publicación: https://care.diabetesjournals.org/content/37/8/2168
  • AWARD-4 (Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/26009229
  • AWARD-5 (Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/25912221
  • AWARD-6 (Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes). Publicación: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60976-4/fulltext
  • AWARD-7 (Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease). Publicación: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30104-9/fulltext
  • AWARD-8 (A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/26799540
  • AWARD-9 (Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/28294499
  • AWARD-10 (Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes). Publicación: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30023-8/fulltext
  • AWARD-11 (Study of the Efficacy and Safety of Investigational Dulaglutide Doses When Added to Metformin in Patients with Type 2 Diabetes Mellitus). Al momento de esta publicación, se ha reportado que los puntos de corte son satisfactorios en cuanto a lograr niveles más bajos de HbA1c a menor plazo, así como mejores valores en la pérdida de peso con las dosis de 3.0 mg y 4.5 mg de Dulaglutide semanal. Se espera que el estudio finalice a finales del 2019.
  • REWIND (Dulaglutide and cardiovascular outcomes in type 2 diabetes). Publicación: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31149-3/fulltext
• Albiglutide
  • HARMONY (Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease). Publicación: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32261-X/fulltext
  • HARMONY-2 (Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide, 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise). Publicación: https://link.springer.com/article/10.1007/s00125-015-3795-1
  • HARMONY-3 (104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin). Publicación:
  • HARMONY-4 (randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea). Publicación: https://link.springer.com/article/10.1007/s00125-014-3360-3
  • HARMONY-5 ( year 3 results: albiglutide vs placebo and vs pioglitazone in triple therapy (background metformin and glimepiride) in people with type 2 diabetes). Este es el abstract al tercer año de estarse corriendo el estudio: https://easddistribute.m-anage.com/from.storage?image=bOIj7gcyILrLfrT9A4QWrz%2bSOSoHt9yjh91wvQFsmqK6WDEfRl7o%2fy0qPsYtR8quSHojFu2MJVTZ7sZVMx594Q%3d%3d
  • HARMONY-6 (Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro). Publicación: https://www.ncbi.nlm.nih.gov/pubmed/24898300
  • HARMONY-7 (Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs). Publicación: https://www.thelancet.com/journals/landa/article/PIIS2213-8587(13)70214-6/fulltext
  • HARMONY-8 (Once Weekly GLP1 Agonist Albiglutide vs. Sitagliptin in Type 2 Diabetes Patients With Renal Impairment: Week 26 Results). Publicación: https://link.springer.com/article/10.1007/s12467-013-0029-3
• Semaglutide
  • PIONEER-1 (Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes). Publicación: https://doi.org/10.2337/dc19-0749
  • PIONEER-2 (Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin). Publicación: https://doi.org/10.2337/dc19-0883
  • PIONEER-3 (Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea). Publicación: 10.1001/jama.2019.2942
  • PIONEER-4 (Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes). Publicación: Lancet 2019;394:39-50.
  • PIONEER-5 (Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment). Publicación: https://doi.org/10.1016/S2213-8587(19)30192-5
  • PIONEER-6 (Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes). Publicación: https://www.nejm.org/doi/10.1056/NEJMoa1901118
  • PIONEER-7 (Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes). Publicación: 10.1016/S2213-8587(19)30194-9
  • PIONEER-8 (Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes). Publicación: https://doi.org/10.2337/dc19-0898
  • SUSTAIN-1 (Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes). Publicación: 10.1016/S2213-8587(17)30013-X
  • SUSTAIN-2 (Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes. Publicación: 10.1016/S2213-8587(17)30092-X
  • SUSTAIN-3 (Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes). Publicación: 10.2337/dc17-0417
  • SUSTAIN-4 (Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes). Publicación: 10.1016/S2213-8587(17)30085-2
  • SUSTAIN-5 (Semaglutide Added to Basal Insulin in Type 2 Diabetes). Publicación: 10.1210/jc.2018-00070
  • SUSTAIN-6 (Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes). Publicación: https://www.nejm.org/doi/full/10.1056/NEJMoa1607141
  • SUSTAIN-7 (Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes). Publicación: https://doi.org/10.1016/S2213-8587(18)30024-X
  • SUSTAIN-8 (Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes). Publicación: https://doi.org/10.1016/S2213-8587(19)30311-0
  • SUSTAIN-9 (Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes). Publicación: https://doi.org/10.1016/S2213-8587(19)30066-X
  • SUSTAIN-10 (Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes). Publicación: https://doi.org/10.1016/j.diabet.2019.101117
  • SUSTAIN 11 ( Effect of Semaglutide Once-weekly Versus Insulin Aspart Three Times Daily, Both as Add on to Metformin and Optimised Insulin Glargine (U100) in Subjects With Type 2 Diabetes) Fecha estimada de finalización: 22 de febrero del 2021. datos disponibles: https://clinicaltrials.gov/ct2/show/NCT03689374
• Lixisenatide
  • GetGoal-Mono (Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes). Publicación: 10.2337/dc11-1935
  • GetGoal-Mono Japan (Long-term safety of once-daily lixisenatide in Japanese patients with type 2 diabetes mellitus). Publicación: 10.1016/j.jdiacomp.2015.07.003
  • GetGoal-M (Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin). Publicación: 10.2337/dc12-2006
  • GetGoal-M-Asia (Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea). Publicación: 10.1002/dmrr.2541
  • GetGoal-F1 (Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin). Publicación: 10.1111/dme.12328
  • GetGoal-P (Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone). Publicación: 10.1111/dom.12121
  • GetGoal-S (Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in Type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin). Publicación: 10.1016/j.jdiacomp.2014.01.012
  • GetGoal-X (Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin). Publicación: 10.2337/dc12-2709
  • GetGoal-L (Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin). Publicación: 10.2337/dc12-2454
  • GetGoal-Duo 1 (Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine). Publicación: 10.2337/dc12-2462
  • GetGoal-L-Asia (Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea). Publicación: 10.1111/j.1463-1326.2012.01618.x
• Exenatide
  • DURATION-1 (Comparison of once-weekly with twice-daily exenatide in the treatment of type 2 diabetes). Publicación: 10.1517/14656566.2010.497142
  • DURATION-2 (efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once‐weekly exenatide). Publicación: https://doi.org/10.1111/j.1464-5491.2011.03301.x
  • DURATION-3 (Exenatide once weekly versus insulin glargine for type 2 diabetes). Publicación: 10.1016/S2213-8587(14)70029-4
  • DURATION-4 (Efficacy and Safety of Exenatide OnceWeekly Versus Metformin, Pioglitazone,and Sitagliptin Used as Monotherapy inDrug-Naive Patients With Type 2Diabetes). Publicación: https://www.researchgate.net/publication/51973878_Efficacy_and_Safety_of_Exenatide_Once_Weekly_Versus_Metformin_Pioglitazone_and_Sitagliptin_Used_as_Monotherapy_in_Drug-Naive_Patients_With_Type_2_Diabetes_DURATION-4
  • DURATION-5 (Safety and tolerability of exenatide once weekly in patients with type 2 diabetes). Publicación: 10.2147/DMSO.S77290
  • DURATION-6 (Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes). Publicación: 10.1016/S0140-6736(12)61267-7
  • DURATION-7 (Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes). Publicación: 10.1111/dom.13266
  • DURATION-8 (Hormone-substrate changes with exenatide plus dapagliflozin versus each drug alone). Publicación: 10.1111/dom.13870